Periodontal, maxillo-facial and orthopedic procedures frequently entail bone grafting. A satisfactory clinical result is, however, not always achieved even when the best current implant materials are used. For example, a poor result may be anticipated when the graft site is fibrotic or irradiated, or if sterilized bone bank bone is used. The studies described in this application are directed toward the development of a composite graft material which will work well in both routine and difficult-to-treat circumstances. Initially, composite grafts consisting of native autologous bone or demineralized or freeze-dried allogeneic bone matrices, with and without autologous marrow cells, will be implanted into fresh and chronic (fibrosed) experimental osteotomy sites located in the long bones and periodontium of rabbits. In some studies, the graft bed will be irradiated to destroy the local population of osteoprogenitor cells. Healing will be evaluated using quantitative histomorphometric methods. The onset and progress of graft revascularization will be established by the Hydrogen Washout Technique. In an important related series of studies, we plan to critically evaluate the nature of the osteoprogenitor cell populations of marrow and some soft tissues. We will employ Friedenstein's techniques to grow, in vitro, populations of Determined Osteogenic Precuror Cells (DOPCs) and Inducible Osteogenic Precursor Cells (IOPCs) isolated from marrow. These cells will then be combined with a number of graft bone substrates (fresh autologous, demineralized and freeze-dried allogeneic bone) and implanted into normal and irradiated skeletal tissue beds to determine the relative participation of the grafted OPCs vs the OPCs at the graft site in bony reconstruction. Similar trials will be carried out with IOPCs derived from cultures of blood and skin biopsies.